Based on the technique developed in our laboratory which made possible the reconstruction of replicating cells from isolated nuclei and enucleated cells using the human diploid fibroblast WI-38, future work can approach the following important areas: (1) the genetic analysis of aging by transferring specific chromosomes into "young" and "old" cells. This will involve karyotyping of the finite life span cells, studies of DNA and RNA synthesis in the present cultures, and then reexamination of the cells after chromosomal and nuclear transfer. The WI-38 and WI-26 fibroblast cells will be used for this study. (2) Studies on the aging cell membrane and specific protein synthetic activities, using cells with specific HLA determinants on their cell membranes. Preliminary studies have already produced cells whose cytoplasts and nuclei differ in cell surface determinants. (3) The ability to alter the finite life span of a cell by the addition of "malignant" or transformed cell nuclei. Hopefully, this may furnish data on our ability to influence both the nucleus and cytoplasm of the finite cell and, if appropriate reconstructions are made, the factors controlling "finite" or "infinite" cell states. The development of the techniques for analysis of the biosynthetic potentials of cells on microscale, using labeled precursors and autoradiography, will enable the study of a small number of cells, such as those obtained by reconstruction or by prolonged culturing of Phase III cells. Special emphasis will be put on the effects of aging on the lipid biosynthesizing ability, reflecting possible changes in membrane properties.